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Olivier Lespinet

Publications and source records attributed to Olivier Lespinet.

8 recordsLinked to original sources
PubMed2006

ORENZA: a web resource for studying ORphan ENZyme activities.

BACKGROUND: Despite the current availability of several hundreds of thousands of amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in major public databases. This wide gap separating knowledge of biochemical function and sequence information is found for nearly all classes of enzymes. Thus, there is an urgent need to explore these sequence-less EC numbers, in order to progressively close this gap. DESCRIPTION: We designed ORENZA, a PostgreSQL database of ORphan ENZyme Activities, to collate information about the EC numbers defined by the NC-IUBMB with specific emphasis on orphan enzyme activities. Complete lists of all EC numbers and of orphan EC numbers are available and will be periodically updated. ORENZA allows one to browse the complete list of EC numbers or the subset associated with orphan enzymes or to query a specific EC number, an enzyme name or a species name for those interested in particular organisms. It is possible to search ORENZA for the different biochemical properties of the defined enzymes, the metabolic pathways in which they participate, the taxonomic data of the organisms whose genomes encode them, and many other features. The association of an enzyme activity with an amino acid sequence is clearly underlined, making it easy to identify at once the orphan enzyme activities. Interactive publishing of suggestions by the community would provide expert evidence for re-annotation of orphan EC numbers in public databases. CONCLUSION: ORENZA is a Web resource designed to progressively bridge the unwanted gap between function (enzyme activities) and sequence (dataset present in public databases). ORENZA should increase interactions between communities of biochemists and of genomicists. This is expected to reduce the number of orphan enzyme activities by allocating gene sequences to the relevant enzymes.

Amino Acid Sequence↗
PubMed2006

Orphan enzymes could be an unexplored reservoir of new drug targets.

Despite the immense progress of genomics, and the current availability of several hundreds of thousands of amino acid sequences, >39% of well-defined enzyme activities (as represented by enzyme commission, EC, numbers) are not associated with any sequence. There is an urgent need to explore the 1525 orphan enzymes (enzymes having EC numbers without an associated sequence) to bridge the wide gap that separates knowledge of biochemical function and sequence information. Strikingly, orphan enzymes can even be found among enzymatic activities successfully used as drug targets. Here, knowledge of sequence would help to develop molecular-targeted therapies, suppressing many drug-related side-effects.

Animals↗
PubMed2005

Orphan enzymes?

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed2002

Characterisation of two snail genes in the gastropod mollusc Patella vulgata. Implications for understanding the ancestral function of the snail-related genes in Bilateria.

Snail genes have been found to play a role in mesoderm formation in two of the three clades of bilaterians, deuterostomes (comprising the chordates) and ecdysozoans (comprising the arthropods). No clear data are available on the role these genes play in development of the mesoderm in the third clade, that of lophotrochozoans (comprising annelids and molluscs). We identified two new members of the snail gene family in the gastropod mollusc Patella vulgata. Phylogenetic analysis showed that the two genes clearly belong to the snail sub-family. Their expression patterns do not indicate a role during early mesoderm formation. In fact, contrary to expectations, the snail genes of Patella were mostly expressed in the ectoderm. In view of the location of their expression sites, we suggest that these genes could be involved in regulating epithelial-mesenchymal transitions (EMT) and cell motility, as has recently been demonstrated for snail genes in vertebrates. This may well correspond to the ancestral function of these genes. The results are discussed in the light of the evolutionary origin of the mesoderm. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00427-002-0228-1.

Amino Acid Sequence↗
PubMed2002

The role of lineage-specific gene family expansion in the evolution of eukaryotes.

A computational procedure was developed for systematic detection of lineage-specific expansions (LSEs) of protein families in sequenced genomes and applied to obtain a census of LSEs in five eukaryotic species, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the green plant Arabidopsis thaliana. A significant fraction of the proteins encoded in each of these genomes, up to 80% in A. thaliana, belong to LSEs. Many paralogous gene families in each of the analyzed species are almost entirely comprised of LSEs, indicating that their diversification occurred after the divergence of the major lineages of the eukaryotic crown group. The LSEs show readily discernible patterns of protein functions. The functional categories most prone to LSE are structural proteins, enzymes involved in an organism's response to pathogens and environmental stress, and various components of signaling pathways responsible for specificity, including ubiquitin ligase E3 subunits and transcription factors. The functions of several previously uncharacterized, vastly expanded protein families were predicted through in-depth protein sequence analysis, for example, small-molecule kinases and methylases that are expanded independently in the fly and in the nematode. The functions of several other major LSEs remain mysterious; these protein families are attractive targets for experimental discovery of novel, lineage-specific functions in eukaryotes. LSEs seem to be one of the principal means of adaptation and one of the most important sources of organizational and regulatory diversity in crown-group eukaryotes.

Animals↗
PubMed2002

Expression pattern of Brachyury in the mollusc Patella vulgata suggests a conserved role in the establishment of the AP axis in Bilateria.

We report the characterisation of a Brachyury ortholog (PvuBra) in the marine gastropod Patella vulgata. In this mollusc, the embryo displays an equal cleavage pattern until the 32-cell stage. There, an inductive event takes place that sets up the bilateral symmetry, by specifying one of the four initially equipotent vegetal macromeres as the posterior pole of all subsequent morphogenesis. This macromere, usually designated as 3D, will subsequently act as an organiser. We show that 3D expresses PvuBra as soon as its fate is determined. As reported for another mollusc (J. D. Lambert and L. M. Nagy (2001) Development 128, 45-56), we found that 3D determination and activity also involve the activation of the MAP kinase ERK, and we further show that PvuBra expression in 3D requires ERK activity. PvuBra expression then rapidly spreads to neighbouring cells that cleave in a bilateral fashion and whose progeny will constitute the posterior edge of the blastopore during gastrulation, suggesting a role for PvuBra in regulating cell movements and cleavage morphology in Patella. Until the completion of gastrulation, PvuBra expression is maintained at the posterior pole, and along the developing anterior-posterior axis. Comparing this expression pattern with what is known in other Bilateria, we advocate that Brachyury might have a conserved role in the regulation of anterior-posterior patterning among Bilateria, through the maintenance of a posterior growth zone, suggesting that a teloblastic mode of axis formation might be ancestral to the Bilateria.

Amino Acid Sequence↗
PubMedDate not supplied

A lophotrochozoan twist gene is expressed in the ectomesoderm of the gastropod mollusk Patella vulgata.

The twist gene is known to be involved in mesoderm formation in two of the three clades of bilaterally symmetrical animals: viz. deuterostomes (such as vertebrates) and ecdysozoans (such as arthropods and nematodes). There are currently no data on the spatiotemporal expression of this gene in the third clade, the lophotrochozoans (such as mollusks and annelids). To approach the question of mesoderm homology across bilaterians, we decided to analyze orthologs of this gene in the gastropod mollusk Patella vulgata that belongs to the lophotrochozoans. We present here the cloning, characterization, and phylogenetic analysis of a Patella twist ortholog, Pv-twi, and determine the early spatiotemporal expression pattern of this gene. Pv-twi expression was found in the trochophore larva in a subset of the ectomesoderm, one of the two sources of mesoderm in Patella. These data support the idea that twist genes were ancestrally involved in mesoderm differentiation. The absence of Pv-twi in the second mesodermal source, the endomesoderm, suggests that also other genes must be involved in lophotrochozoan mesoderm differentiation. It therefore remains a question if the mesoderm of all bilaterians is homologous.

Amino Acid Sequence↗